Targeting heterogeneous tumor microenvironments in pancreatic cancer mouse models of metastasis by TGF-β depletion.

The dual tumor-suppressive and -promoting functions of TGF-β signaling has made its targeting challenging. We examined the effects of TGF-β depletion by AVID200/BMS-986416 (TGF-β-TRAP), a TGF-β ligand trap, on the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) murine models with different organ-specific metastasis. Our study demonstrated that TGF-β-TRAP potentiates the efficacy of anti-programmed cell death 1 (anti-PD-1) in a PDAC orthotopic murine model with liver metastasis tropism, significantly reducing liver metastases.

Patient-derived Organoid Pharmacotyping As A Predictive Tool for Therapeutic Selection in Pancreatic Ductal Adenocarcinoma.

Objective: We integrate a new approach to chemosensitivity data for clinically-relevant regimen matching, and demonstrate the relationship with clinical outcomes in a large PDO biobank.

Summary Background Data: Pancreatic ductal adenocarcinoma (PDAC) usually recurs following potentially curative resection. Prior studies related patient-derived organoid (PDO) chemosensitivity with clinical responses.

Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells.

CLDN18.2 BiTE Engages Effector and Regulatory T Cells for Antitumor Immune Response in Preclinical Models of Pancreatic Cancer.

Background & Aims: BiTE (bispecific T-cell engager) immune therapy has demonstrated clinical activity in multiple tumor indications, but its influence in the tumor microenvironment remains unclear. CLDN18.2 is overexpressed in solid tumors including gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC), both of which are characterized by the presence of immunosuppressive cells, including regulatory T cells (Tregs) and few effector T cells (Teffs).

CCR2/CCR5 inhibitor permits the radiation-induced effector T cell infiltration in pancreatic adenocarcinoma.

The resistance of pancreatic ductal adenocarcinoma (PDAC) to immune checkpoint inhibitors (ICIs) is attributed to the immune-quiescent and -suppressive tumor microenvironment (TME). We recently found that CCR2 and CCR5 were induced in PDAC following treatment with anti-PD-1 antibody (αPD-1); thus, we examined PDAC vaccine or radiation therapy (RT) as T cell priming mechanisms together with BMS-687681, a dual antagonist of CCR2 and CCR5 (CCR2/5i), in combination with αPD-1 as new treatment strategies. Using PDAC mouse models, we demonstrated that RT followed by αPD-1 and prolonged treatment with CCR2/5i conferred better antitumor efficacy than other combination treatments tested.

Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response.

Purpose: Patient-derived organoids (PDO) are a promising technology to support precision medicine initiatives for patients with pancreatic ductal adenocarcinoma (PDAC). PDOs may improve clinical next-generation sequencing (NGS) and enable rapid ex vivo chemotherapeutic screening (pharmacotyping).

Experimental Design: PDOs were derived from tissues obtained during surgical resection and endoscopic biopsies and studied with NGS and pharmacotyping.

Evaluation of National Resident Matching Program and Electronic Residency Application Service Data in the Integrated Plastic Surgery Match.

Introduction: The National Resident Matching Program and Electronic Residency Application Service provide data for tracking trends among applicants in each specialty over the past 5 years. The purpose of this study was to examine this information and determine sex and race/ethnicity distribution over the past 5 years.

Methods: The National Resident Matching Program and Electronic Residency Application Service databases were surveyed for trends in the following categories: number of positions, number of applicants, percent of applicants per position, and number of applicants by sex and self-identified race/ethnicity.

Does etiology of gastroparesis determine clinical outcomes in gastric electrical stimulation treatment of gastroparesis?

Background: Gastroparesis is a condition characterized by impaired gastric motility that may result in weight loss and malnutrition. There have been promising studies demonstrating improvement in symptoms after gastric electrical stimulation (GES) implantation for medically refractory gastroparetics [1-10]. With the heterogeneous population of gastroparetics, the aim of this study was to assess if etiology correlated with response to GES.

The Past, Present, and Future in Management of Small Renal Masses.

Management of small renal masses (SRMs) is currently evolving due to the increased incidence given the ubiquity of cross-sectional imaging. Diagnosing a mass in the early stages theoretically allows for high rates of cure but simultaneously risks overtreatment. New consensus guidelines and treatment modalities are changing frequently.